Professor of Neurobiology and Anatomy

B.A. University of California, Berkeley

Ph.D. University of California, San Diego

Molecular Biology Program

Developmental Neurobiology

Research

During development of the central nervous system (CNS), cells are influenced by their
environment to adopt specific fates. These environmental signals are crucial for
the correct patterning of cell types and their subsequent functional connections.
My laboratory is studying the role of the Wnt/β-catenin signaling pathway in CNS
cell fate specification. We use zebrafish as a model organism, focusing on the regulation
of Wnt/β-catenin target genes in the CNS by a family of transcription factors called
Tcf proteins. Tcfs are required for β-catenin to regulate transcription, and can
act as repressors or activators of target genes depending on the state of Wnt signaling.

SPINAL CORD NEUROGENESIS

We are interested in the functions of Wnt signaling in zebrafish spinal cord development
and regeneration. We have shown that following transection of the larval spinal cord,
Wnt signaling is required for radial glia to generate new neurons. One current project
in the lab is determining the mechanism downstream of Wnt signaling that mediates
neurogenesis following injury. This function may be critical for stem cell-mediated
regeneration. A second project is investigating whether new neurons integrate into
functional circuitry, and whether they are required for the recovery of sensory and
motor behavior.

HYPOTHALAMIC NEUROGENESIS

This work focuses on the role of Wnt signaling and its transcriptional mediator Lef1
in the differentiation of neural progenitors in the posterior hypothalamus. This region
of the brain maintains Wnt activity and continues to produce neurons throughout life,
suggesting that Wnt-regulated neurogenesis plays an important role in the adult brain.
We have found an evolutionarily conserved requirement for Lef1 in mediating anxiety,
and in the formation of anxiolytic hypothalamic neurons. We have also identified Lef1
target genes in the zebrafish and mouse hypothalamus, and are determining their functions
in neurogenesis and behavior. Other work is focused on testing the requirement for
postembryonic neurogenesis in modulating anxiety.

References

Xie, Y., and Dorsky, R.I. (2017). Development of the hypothalamus: conservation, modification and innovation. Development 144, 1588-1599.